Okebo
OKEBO- doxycycline capsule
Encore Dermatology Inc.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Okebo and other antibacterial drugs, Okebo should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
DESCRIPTION
Doxycycline is a broad-spectrum antibacterial synthetically derived from oxytetracycline. Okebo (Doxycycline monohydrate USP) Capsules, 100 mg, 75 mg, and 50 mg capsules contain doxycycline monohydrate equivalent to 100 mg, 75 mg, or 50 mg of doxycycline for oral administration. The chemical designation of the light-yellow crystalline powder is alpha-6-deoxy-5-oxytetracycline.
Structural formula:
Doxycycline has a high degree of lipid solubility and a low affinity for calcium binding. It is highly stable in normal human serum. Doxycycline will not degrade into an epianhydro form.
Inert ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose and sodium starch glycolate Type A Potato. Hard gelatin capsule contains black iron oxide, gelatin, red iron oxide, titanium dioxide and yellow iron oxide. The capsules are printed with edible ink containing black iron oxide, potassium hydroxide, propylene glycol, shellac and titanium dioxide.
CLINICAL PHARMACOLOGY
Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in a biologically active form. Doxycycline is virtually completely absorbed after oral administration.
Following a 200 mg dose of doxycycline monohydrate, 24 normal adult volunteers averaged the following serum concentration values:
| Time (hr): | 0.5 | 1.0 | 1.5 | 2.0 | 3.0 | 4.0 | 8.0 | 12.0 | 24.0 | 48.0 | 72.0 |
| Conc. | 1.02 | 2.26 | 2.67 | 3.01 | 3.16 | 3.03 | 2.03 | 1.62 | 0.95 | 0.37 | 0.15 (mcg/mL) |
| Average Observed Values | |
| Maximum Concentration | 3.61 mcg/mL (± 0.9 sd) |
| Time of Maximum Concentration | 2.60 hr (± 1.10 sd) |
| Elimination Rate Constant | 0.049 per hr (± 0.030 sd) |
| Half-Life | 16.33 hr (± 4.53 sd) |
Excretion of doxycycline by the kidney is about 40%/72 hours in individuals with normal function (creatinine clearance about 75 mL/min). This percentage excretion may fall as low as 1 to 5%/72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 mL/min). Studies have shown no significant difference in serum half-life of doxycycline (range 18 to 22 hours) in individuals with normal and severely impaired renal function.
Hemodialysis does not alter serum half-life.
Microbiology
Mechanism of Action
Doxycycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. Doxycycline has bacteriostatic activity against a broad range of Gram-positive and Gram-negative bacteria.
Resistance:
Cross resistance with other tetracyclines is common.
Antimicrobial Activity
Doxycycline has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections (see INDICATIONS AND USAGE).
Gram-Negative Bacteria
Acinetobacter species
Bartonella bacilliformis
Brucella species
Enterobacter aerogenes
Escherichia coli
Francisella tularensis
Haemophilus ducreyi
Haemophilus influenzae
Klebsiella granulomatis
Klebsiella species
Neisseria gonorrhoeae
Shigella species
Vibrio cholerae
Vibrio fetus
Yersinia pestis
Gram-Positive Bacteria
Bacillus anthracis
Listeria monocytogenes
Streptococcus pneumoniae
Anaerobes
Clostridium species
Fusobacterium fusiforme
Propionibacterium acnes
Other Bacteria
Nocardiae and other aerobic Actinomyces species
Borrelia recurrentis
Chlamydophila psittaci
Chlamydia trachomatis
Mycoplasma pneumoniae
Rickettsiae
Treponema pallidum
Treponema pallidum subspecies pertenue
Ureaplasma urealyticum
Parasites
Balantidium coli
Entamoeba species
Plasmodium falciparum *
* Doxycycline has been found to be active against the asexual erythrocytic forms of Plasmodium falciparum , but not against the gametocytes of P. falciparum. The precise mechanism of action of the drug is not known.
Susceptibility Testing Methods
When available, the clinical microbiology laboratory should provide cumulative reports of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.
Dilution Techniques:
Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method (broth and/or agar).1,2,4,6,7 The MIC values should be interpreted according to criteria provided in Table 1.
Diffusion Techniques
Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standard test method.1,3,4 This procedure uses paper disks impregnated with 30 mcg doxycycline to test the susceptibility of bacteria to doxycycline. The disk diffusion interpretive criteria are provided in Table 1.
Anaerobic TechniquesFor anaerobic bacteria, the susceptibility to doxycycline can be determined by a standardized test method.1, 5 The MIC values obtained should be interpreted according to the criteria provided in Table 1.
| * Organisms susceptible to tetracycline are also considered susceptible to doxycycline. However, some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline. † The current absence of resistance isolates precludes defining any results other than “Susceptible”. If isolates yielding MIC results other than susceptible, they should be submitted to a reference laboratory for further testing. ‡ Gonococci with 30 mcg tetracycline disk zone diameters of <19 mm usually indicate a plasmid-mediated tetracycline resistant Neisseria gonorrhoeae isolate. Resistance in these strains should be confirmed by a dilution test (MIC ≥ 16 mcg/mL). | |||||||||
| Bacteria * | Minimal Inhibitory Concentration (mcg/mL) | Zone Diameter (mm) | Agar Dilution (mcg/mL) | ||||||
| S | I | R | S | I | R | S | I | R | |
| Acinetobacter spp. | |||||||||
| Doxycycline | ≤4 | 8 | ≥16 | ≥13 | 10 to 12 | ≤9 | – | – | – |
| Tetracycline | ≤4 | 8 | ≥16 | ≥15 | 12 to 14 | ≤11 | – | – | – |
| Anaerobes | |||||||||
| Tetracycline | – | – | – | – | – | – | ≤4 | 8 | ≥16 |
| Bacillus anthracis † | |||||||||
| Doxycycline | ≤1 | – | – | – | – | – | – | – | – |
| Tetracycline | ≤1 | – | – | – | – | – | – | – | – |
| Brucella species † | |||||||||
| Doxycycline | ≤1 | – | – | – | – | – | – | – | – |
| Tetracycline | ≤1 | – | – | – | – | – | – | – | – |
| Enterobacteriaceae | |||||||||
| Doxycycline | ≤4 | 8 | ≥16 | ≥14 | 11 to 13 | ≤10 | – | – | – |
| Tetracycline | ≤4 | 8 | ≥16 | ≥15 | 12 to 14 | ≤11 | – | – | – |
| Franciscella tularensis † | |||||||||
| Doxycycline | ≤4 | – | – | – | – | – | – | – | – |
| Tetracycline | ≤4 | – | – | – | – | – | – | – | – |
| Haemophilus influenzae | |||||||||
| Tetracycline | ≤2 | 4 | ≥8 | ≥29 | 26 to 28 | ≤25 | – | – | – |
| Mycoplasma pneumoniae † | |||||||||
| Tetracycline | – | – | – | – | – | – | ≤2 | – | – |
| Neisseria gonorrhoeae ‡ | |||||||||
| Tetracycline | – | – | – | ≥38 | 31 to 37 | ≤30 | ≤0.25 | 0.5 to 1 | ≥2 |
| Norcardiae and other aerobic Actinomyces species | |||||||||
| Doxycycline | ≤1 | 2 to 4 | ≥8 | – | – | – | – | – | – |
| Streptococcus pneumoniae | |||||||||
| Doxycycline | ≤ 0.25 | 0.5 | > 1 | > 28 | 25 to 27 | < 24 | – | – | – |
| Tetracycline | <1 | 2 | > 4 | > 28 | 25 to 27 | < 24 | – | – | – |
| Vibrio cholerae | |||||||||
| Doxycycline | ≤4 | 8 | ≥16 | – | – | – | – | – | – |
| Tetracycline | ≤4 | 8 | ≥16 | – | – | – | – | – | – |
| Yersinia pestis | |||||||||
| Doxycycline | ≤4 | 8 | ≥16 | – | – | – | – | – | – |
| Tetracycline | ≤4 | 8 | ≥16 | – | – | – | – | – | – |
| Ureaplasma urealyticum | |||||||||
| Tetracycline | – | – | – | – | – | – | ≤1 | – | ≥2 |
A report of Susceptible (S) indicates that the antimicrobial is likely to inhibit growth of the microorganism if the antimicrobial drug reaches the concentration usually achievable at the site of infection. A report of Intermediate (I) indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug product is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of Resistant (R) indicates that the antimicrobial drug is not likely to inhibit growth of the microorganism if the antimicrobial drug reaches the concentrations usually achievable at the infection site; other therapy should be selected.
Quality ControlStandardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test.1,2,3,4,5,6,7 Standard doxycycline and tetracycline powders should provide the following range of MIC values noted in Table 2. For the diffusion technique using the 30 mcg doxycycline disk or 30 mcg tetracycline disk, the criteria in should be achieved.
| * ATCC is the American Type Culture Collection | |||
| QC Strain | Minimal Inhibitory Concentration (mcg/mL) | Zone Diameter (mm) | Agar Dilution (mcg/mL) |
| Escherichia coli ATCC 25922 | |||
| Doxycycline | 0.5 to 2 | 18 to 24 | – |
| Tetracycline | 0.5 to 2 | 18 to 25 | – |
| Eggerthella lenta ATCC 43055 | |||
| Doxycycline | 2 to 16 | – | – |
| Haemophilus influenzae ATCC 49247 | |||
| Tetracycline | 4 to 32 | 14 to 22 | – |
| Neisseria gonorrhoeae ATCC 49226 | |||
| Tetracycline | – | 30 to 42 | 0.25 to 1 |
| Staphylococcus aureus ATCC 25923 | |||
| Doxycycline | – | 23 to 29 | – |
| Tetracycline | – | 24 to 30 | – |
| Staphylococcus aureus ATCC 29213 | |||
| Doxycycline | 0.12 to 0.5 | – | – |
| Tetracycline | 0.12 to 1 | – | – |
| Streptococcus pneumoniae ATCC 49619 | |||
| Doxycycline | 0.015 to 0.12 | 25 to 34 | – |
| Tetracycline | 0.06 to 0.5 | 27 to 31 | – |
| Bacteroides fragilis ATCC 25285 | |||
| Tetracycline | – | – | 0.12 to 0.5 |
| Bacteroides thetaiotaomicron ATCC 29741 | |||
| Doxycycline | 2 to 8 | – | – |
| Tetracycline | – | – | 8 to 32 |
| Mycoplasma pneumoniae ATCC 29342 | |||
| Tetracycline | 0.06 to 0.5 | – | 0.06 to 0.5 |
| Ureaplasma urealyticum ATCC 33175 | |||
| Tetracycline | – | – | ≥ 8 |
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